The clinical development of novel therapeutic antibodies requires the evaluation of their potential immunogenicity by appropriate assays (Kaliyaperumal, A. and Jing, S., Curr. Pharm. Biotechnol. 10 (2009) 352-358). The anti-drug antibody (ADA) testing usually involves a two tier approach: (1) assays for ADA detection and (2) assays for ADA characterization. ADA detection assays include screening and specificity confirmation (confirmatory) assays. Microtiter plate-based enzyme-linked immunosorbent assays (ELISAs) are still the most widely used format to screen for ADAs due to their high-throughput efficiency, relative simplicity and high sensitivity (Geng, D., et al., J. Pharm. Biomed. Anal. 39 (2005) 364-375). ADA ELISAs are most often designed in a bridge format which provides high selectivity, detection of all isotypes and pan-species ADA detection capability (Mire-Sluis, A. R., et al., J. Immunol. Methods 289 (2004) 1-16).
A bridging ELSA has been developed and used as a screening and confirmation ADA assay for the anti-IL6R antibody tocilizumab (Stubenrauch, K., et al., Clin. Ther. 32 (2010) 1597-1609).
Stubenrauch, K., et al. report a generic anti-drug antibody assay with drug tolerance in serum samples from mice exposed to human antibodies (Anal. Biochem. 430 (2012) 193-199). Bourdage, J. S., et al. report the effect of double antigen bridging immunoassay format on antigen coating concentration dependence and implications for designing immunogenicity assays for monoclonal antibodies (J. Pharm. Biochem. Anal. 39 (2005) 685-690). Mikulskis, A., et al. report solution ELISA as a platform of choice for development of robust, drug tolerant immunogenicity assays in support of drug development (J. Immunol. Meth. 365 (2010) 38-49). Pan, J., et al. report the comparison of the NIDSA® rapid assay with ELISA methods in immunogenicity testing of two biotherapeutics (J. Pharm. Tox. Meth. 63 (2010) 150-159.
In WO 2009/077127 a distinguishing assay is reported.
Qiu, Z. J., et al. report a novel homogeneous biotin-digoxigenin based assay for the detection of human anti-therapeutic antibodies in autoimmune serum (J. Immunol. Meth. 362 (2010) 101-111).